Marci Nilsen, PhD, RN, Receives NIH R37 MERIT Award to Study Radiation-Induced Treatment Toxicity in Head and Neck Cancer Patients
August 8, 2023
Congratulations to Marci Nilsen, PhD, RN, assistant professor in the University of Pittsburgh School of Nursing and the Department of Otolaryngology, for receiving a prestigious National Institutes of Health (NIH) R37 Method to Extend Research in Time (MERIT) award that will further her research into head and neck cancer survivorship and treatment-related toxicities and morbidities, specifically how radiation-induced fibrosis impacts patients longitudinally.
In 2016, Dr. Nilsen, in partnership with the Department of Otolaryngology and former department chair Jonas T. Johnson, MD, created the UPMC Head and Neck Cancer Survivorship Clinic, which at the time was one of the very first such multidisciplinary clinics in the U.S. dedicated to caring for the unique needs of head and neck cancer (HNC) survivors.
The Clinic addresses the numerous challenges, and long-term care needs that head and neck cancer survivors face, beginning at the time of diagnosis and following patients throughout their lives. The clinic’s care model incorporates swallowing therapy, dental health, audiology, physical therapy, and, most recently, a dedicated dietician. The Clinic's approach has been shaped by the clinical learnings and research conducted by Dr. Nilsen and colleagues that has led to the understanding that seeing patients at any stage of their disease, not exclusively directly after treatment, can be life-altering and significantly impact long-term outcomes and quality of life.
Dr. Nilsen's work with HNC survivors has spurred numerous lines of research, grants, and published studies bringing to light the various consequences of head and neck cancer on patients, the long-term effects of HNC and its treatments, and how to improve long-term care and symptom management in survivors.
Rising Rates of HNC
Head and neck cancers constitute the sixth leading cause of cancer worldwide, and there are approximately 60,000 new cases diagnosed annually in the United States. Most new cases are diagnosed as late-stage disease and typically have been associated with older adults — over 50. However, human papillomavirus-associated cases of HNC are increasing, leading to more cases in general and significantly more HNC being diagnosed in younger individuals.
The burdens of these cancers for afflicted patients are significant, from diagnosis through treatment to posttreatment survivorship. The physical, emotional, psychological, and financial implications of a head and neck cancer diagnosis tend to be overwhelming for many, and they persist long after the diagnosis and initial therapies have been provided.
Even if cured from a primary disease standpoint, HNC can leave lasting and severe morbidities and quality-of-life issues for patients primarily due to treatment-related toxicities. Chief among these toxicities is radiation-induced effects.
Radiation-Induced Toxicities Are Common
As Dr. Nilsen explains, radiation therapy is a front-line standard of care for many HNC patients. Indeed, the use and intensity of radiotherapy has increased during the last several decades as the utility of the treatment has been studied and proved beneficial.
Because of the increased use and intensity of radiotherapy that many patients are subjected to, the prevalence and severity of treatment-related adverse effects have risen sharply. According to Dr. Nilsen, acute toxicities experienced by HNC patients have grown by 500%. Nearly 90% of HNC patients will experience adverse effects of their treatment.
"Because we have become much better with our treatment approaches, many more HNC patients are living much longer now, so late effects of their treatments and disease must be dealt with and managed," says Dr. Nilsen. "We're really at the beginning of that process – understanding the types of late effects that are likely to be seen in patients, who are most at risk, and how best to treat and manage them long-term."
One of the major concerns and morbidities seen in HNC patients as a result of treatment is radiation-induced fibrosis (RIF), which is the focus of Dr. Nilsen’s new grant
New Grant Aims and Objectives - Mapping the Trajectories of Radiation-Induced Fibrosis in HNC Patients
Previous research and clinical experience by Dr. Nilsen and colleagues have shown that more than half of HNC survivors experience neck disability due to treatment and that this disability tends to worsen long-term, alongside patients experiencing difficulty swallowing. However, there is a substantial gap in the literature about how radiation-induced fibrosis in HNC patients may change over time and how it relates to or compounds other symptoms. This lack of understanding has hindered the development of more effective, customized patient treatments.
Furthermore, there currently is no reliable way to identify which patients are most likely to develop RIF or who may experience the most severe or profound downstream effects. However, initial research suggests that certain microRNAs (miRNAs) might play a role as potential biomarkers for disease trajectory.
Dr. Nilsen’s study will follow a cohort of 334 patients longitudinally, starting before radiation treatment and continuing at several intervals up to two years after receiving radiotherapy for their HNC. The goal is to identify different paths that RIF and its associated side effects can take and what factors influence these paths.
Dr. Nilsen’s study sets out four key objectives. First, it aims to map the progression of radiation-induced fibrosis (RIF) and accompanying side effects, such as neck disability and difficulty swallowing, while also analyzing their relationships. Secondly, the study seeks to identify the unique personal characteristics and cancer-related factors contributing to the variability in RIF and its associated side effects. The third aim is to track the development of RIF and concurrent side effects over 24 months following radiation treatment. Lastly, the study plans to investigate the relationship between circulating microRNAs (miRNAs), tiny molecules in the blood, and the patterns of RIF and associated side effects, potentially identifying them as valuable biomarkers.
“What we hope to accomplish is a much better understanding of RIF and its associated side effects that allows us to begin developing more tailored treatments to minimize the potential for debilitating effects of HNC treatment," says Dr. Nilsen. "If we can establish the most likely patterns for patients and predict accurately which path an individual may follow, we can intervene and plan accordingly."
Further Reading and News
Selection of Prior Published Research
Below is a selection of recent research published by Dr. Nilsen and colleagues related to their work on HNC survivorship and the effects of treatments on patient’s health.
- Trotti A, Pajak TF, Gwede CK, Paulus R, Cooper J, Forastiere A, et al. TAME: development of a new method for summarising adverse events of cancer treatment by the Radiation Therapy Oncology Group. The Lancet Oncology. 2007;8(7):613-24.
- Nilsen, M. L., Mady, L. J., Hodges, J., Wasserman-Wincko, T., & Johnson, J. T. Burden of treatment: Reported outcomes in a head and neck cancer survivorship clinic. The Laryngoscope. 2019; 129(12): E437–E444. https://doi.org/10.1002/lary.27801
- Nilsen, M. L., Lyu, L., Belsky, M. A., Mady, L. J., Zandberg, D. P., Clump, D. A., 2nd, Skinner, H. D., Peddada, S. D., George, S., & Johnson, J. T. Impact of Neck Disability on Health-Related Quality of Life among Head and Neck Cancer Survivors. Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery. 2020; 162(1): 64–72. https://doi.org/10.1177/0194599819883295
- Harris, A., Lyu, L., Wasserman-Winko, T., George, S., Johnson, J. T., & Nilsen, M. L. Neck Disability and Swallowing Function in Posttreatment Head and Neck Cancer Patients. Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery. 2020; 163(4): 763–770. https://doi.org/10.1177/0194599820923630
- Magaña, L. C., Murati, S., Riffitts, M., Harrison, C., Harris, A., Sowa, G., Johnson, J. T., Bell, K., & Nilsen, M. Subjective and Objective Measures in Assessing Neck Disability and Pain in Head and Neck Cancer. The Laryngoscope. 2021; 131(9): 2015–2022. https://doi.org/10.1002/lary.29488
- Harris, A., Branstetter, B., Li, J., Piva, S. R., Johnson, J. T., & Nilsen, M. L. Evaluation of Neck Disability Using Computed-Tomography in Head and Neck Cancer Survivors. Frontiers in Pain Research (Lausanne, Switzerland). 2022; 3, 910247. https://doi.org/10.3389/fpain.2022.910247
- Rhoten, B. A., Murphy, B. A., Dietrich, M. S., & Ridner, S. H. (2018). Depressive symptoms, social anxiety, and perceived neck function in patients with head and neck cancer. Head & Neck. 2018; 40(7): 1443–1452. https://doi.org/10.1002/hed.25129
- Ridner, S. H., Dietrich, M. S., Niermann, K., Cmelak, A., Mannion, K., & Murphy, B. A Prospective Study of the Lymphedema and Fibrosis Continuum in Patients with Head and Neck Cancer. Lymphatic Research and Biology. 2016; 14(4): 198–205. https://doi.org/10.1089/lrb.2016.0001
- Ridner, S. H., Dietrich, M. S., Sonis, S. T., & Murphy, B. Biomarkers Associated with Lymphedema and Fibrosis in Patients with Cancer of the Head and Neck. Lymphatic Research and Biology. 2018; 16(6): 516–524. Advance online publication. https://doi.org/10.1089/lrb.2017.0074
- Nachalon, Y., Nativ-Zeltzer, N., Evangelista, L. M., Dhar, S. I., Lin, S. J., Shen, S. C., & Belafsky, P. C. Cervical Fibrosis as a Predictor of Dysphagia. The Laryngoscope. 2021; 131(3): 548–552. https://doi.org/10.1002/lary.28880
